The present invention relates to filtration devices and methods and, more particularly, to a filtration cartridge and its uses as a hemodiafilter in one application and a fluid filter that produces sterile fluid in another application.
The most common treatment for End Stage Renal Disease (ESRD) essentially consists of a hemodialysis process, wherein blood to be cleaned flows on one side of a semi-permeable membrane and a physiologic solution, a dialysate, flows on the other side of the membrane, whereby toxins in the blood are transferred from one side to the other. The primary driving force in this treatment is diffusion. This process is generally effective in removing small Molecular Weight (MW) toxins such as urea and creatinine. However, this process is much less effective in removing middle range MW substances, e.g., substances having a molecular weight higher than about 1 kDa, because of a low diffusion coefficient of such substances.
To a much lesser extent hemodiafiltration is used as a treatment modality. In hemodiafiltration, diffusion is combined with filtration to remove toxins from the blood. Sterile non-pyrogenic replacement fluid is added to the blood either prior to or after it enters a hemodiafiltration cartridge. The replacement fluid replaces plasma water, which is filtered across the semi-permeable membrane during the hemodiafiltration process. The advantage of hemodiafiltration over hemodialysis is the use of filtration in conjunction with diffusion to remove toxins. As a result of this combination, hemodiafiltration is more efficient at removing small molecules, e.g., creatinine and urea, as well as removing much greater quantities of middle range MW substances, by filtration.
Two primary needs must be met for hemodiafiltration to be effective. The first is for a patient treatment diafilter that allows for high filtration rates and as a result increased clearances of toxins. The second is for a sterilizing filter or series of filters that can provide large volumes of sterile infusion fluid in a continuous manner.
Regarding the first need, state of the art designs for hemodiafilters are substantially equivalent to those of high flux dialyzers. Such filters consist of a bundle of hollow fibers in a cylindrical housing. During operation of the hemodiafiltration system, replacement fluid is injected into the blood either upstream (pre-dilution) or downstream (post-dilution) of the filter cartridge.
Diafiltration devices using pre-dilution or post-dilution schemes have inherent efficiency limitations. Pre-dilution schemes allow for relatively unlimited filtration, however, because the blood is diluted prior to reaching the filter, the overall mass transfer of solutes by diffusion is decreased. In other words, the efficiency of the removal of the toxins is less than desired. Post-dilution schemes have the advantage of keeping blood concentrations high, resulting in more efficient diffusion and convection of solutes, however, the increased concentration of blood cells and the resultant higher blood viscosity during filtration, poses a limit on the amount of water that can be filtered. This is typically limited to approximately 25% of the blood flow.
With respect to the second need, hemodiafiltration requires large volumes of sterile infusion fluid be available, therefore the standard methodology of IV infusion (hanging one liter saline bags) is not appropriate. Instead a method in which sterile fluid is produced in a continuous manner is generally required to satisfy this need.
There are methods where non-sterile infusion fluid for hemodiafiltration is filtered through one or a series of filters to render it sterile before infusion into the patient""s bloodstream. The filtration arrangement in these processes must remove endotoxins, bacteria, and other pyrogen-inducing compounds. If a filter should fail during the process, a patient may suffer a septic or pyrogenic reaction due to inadequately filtered fluid.
Several filtration techniques and devices do currently exist. For example on-line production of substitution fluid is described in D. Limido, et al., xe2x80x9cClinical Evaluation of AK-100 ULTRA for Predilution HF with On-Line Prepared Bicarbonate Substitution Fluid. Comparison with HD and Acetate Postdilution HFxe2x80x9d, International Journal of Artificial Organs, Vol. 20, No. 3 (1997), pp. 153-157. Another sterility filter is described in U.S. Pat. No. 4,784,768 to Mathieu. Most prior art schemes have key drawbacks, they either rely on a single filter to sterilize the fluid or they use two separate filters in series increasing the cost and complexity.
The need exists for a filter that provides redundant sterile filtration and produces physiologic fluid suitable for patient infusion.
In attempting to meet the first need of providing a diafilter that accommodates high filtration rates, one embodiment of the diafilter reduces and/or eliminates the drawbacks of prior art hemodiafiltration devices by providing a scheme in which blood is diluted after it is partially, but not fully, diafiltered. The diafiltration scheme of the present invention combines the benefits of pre-dilution schemes, e.g., high filtration rates, with the benefits of post-dilution schemes, e.g., high diffusive and convective efficiencies. The present diafilter can be adapted to operate in conjunction with conventional diafiltration machines, including but not limited to Fresenius 4008 On-Line Plus, Gambro AK 200 Ultra. Alternatively, the diafilter may be used with conventional hemodialysis machines, including but not limited to, Fresenius 2008H, Baxter SPS 1550, Cobe Centry System 3, etc, that have been modified to provide a source of replacement fluid. For example, a pump or valve meters dialysate from a tee in the main dialysate stream and passes it through sterilizing filters.
When serving as a diafiltration cartridge, the present invention has blood and dialysate inlet and outlet ports. The cartridge includes a single housing, for example, a cylindrical housing, which houses two hemodiafiltration stages, wherein the first stage has a blood inlet and the second stage has a blood outlet. Accordingly, the present invention accomplishes dual-stage diafiltration within a single cylindrical housing having a cylindrical hollow fiber bundle disposed therein. The diafilter thus has the appearance of a traditional dialyzer with the exception that the construction of its two ends or header caps differs from that of a traditional dialyzer design. The first end cap includes both the blood inlet and blood outlet ports separated by an internal wall and seal, which is designed to segregate the filter into first and second diafiltration stages. The second end cap serves as blood/replacement fluid mixing chamber and has an inlet port for receiving substitution fluid.
In the diafilter embodiment of the present invention, the blood inlet and outlet ports are located at a first end of the cartridge. The dialysate outlet is preferably also located at or near the first end of the cartridge. For example, in one exemplary embodiment, the blood inlet and outlet ports and dialysate outlet are located at the top (first end) of the cartridge. The main cylindrical housing contains a longitudinal bundle of high flux semi-permeable hollow fibers sealed off from the dialysate compartments at each end by a potting compound, such as polyurethane. The substitution fluid inlet and the dialysate inlet are located at or near an opposite second end, e.g., the bottom of the cartridge. At the substitution fluid inlet port a sterile replacement fluid is mixed with the partially diafiltered blood. This occurs in a common header region where the blood exits the hollow fibers of the first stage and enters the hollow fibers of the second stage. The dialysate flow is common to the two filter stages and runs counter-current to blood flow in the first stage and co-current to blood flow in the second stage.
The counter-current flow in the first stage keeps a maximum concentration gradient of uremic toxins allowing for high diffusive clearance of small molecular weight (MW) solutes. The co-current dialysate flow in the second stage necessitated by the design of the present cartridge, is acceptable because convective clearances dominate diffusive clearances in this stage. The relative filtration rates of the first and second stages are passively controlled by the effect that hemodilution and hemoconcentration have on the resistance to flow across the membrane in these stages.
After the blood flows through the hollow fibers of the second stage, the blood exits the diafilter through the blood outlet port located at the same end as the blood inlet port.
Another embodiment of the present invention seeks to meet the second need of providing large volumes of sterile infusion fluid. It addresses the shortcomings of prior art by providing serial (redundant) filtration within a single cartridge and single fiber bundle. As a result of the redundancy there is added assurance of sterility and the removal of endotoxin. Due to the single bundle design there is greater simplicity and convenience compared to current state of the art.
The sterility filter embodiment of the cartridge is similar in appearance and function to the diafiltration embodiment with a few exceptions. The sterility filter has a single cylindrical housing with a cylindrical hollow fiber bundle disposed therein. However, only one end cap is necessary for the sterility filter. The cap is a two-port cap with a non-sterile fluid inlet port and sterile fluid outlet port separated by an internal wall and seal that also segregates the filter into primary and redundant filtration stages. At the other end of the device the fiber remains encased with the ends sealed in the potting compound. As a result of this dead-end filtration configuration there is no need for a second end cap.
In the sterility filter embodiment of the cartridge the fluid inlet and outlet ports are located at one end of the device, for example the top. The fluid may be dialysate, which is drawn off as a portion of the machine dialysate flow with the intent to be used as replacement fluid in diafiltration therapy. The ports that serve as dialysate ports in the diafilter embodiment of the cartridge are normally closed off in the sterility filter embodiment. In this embodiment they may be used for priming, testing, or disinfection of the filter.
During operation non-sterile fluid enters the inlet port and the fibers of the first (primary filtration) stage. Because the fiber lumens are closed at the other end, all the fluid is forcibly filtered across the membrane and into the casing (filtration) space. The membrane in this embodiment is such that during filtration it removes endotoxin and all bacteria from the fluid rendering it as sterile infusion quality fluid. The common casing space between the two filtration stages is analogous to the dialysate compartment in the diafilter embodiment. The sterile fluid in the common space is then back-filtered into the fiber lumens of the second (redundant filtration) stage. The sterile fluid then exits the cartridge at the header outlet port. This design advantageously provides the safety of redundant filtration, assuring sterility, in the convenience of a conventional single bundle cartridge.